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Fully Human NKG2D Monoclonal Antibody

Background:
The National Cancer Institute's Experimental Transplantation and Immunology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize human monoclonal antibodies as therapeutic agents.

Technology:
NKG2D is a stimulatory or costimulatory receptor located on the cell surface of natural killer (NK) cells and CD8+ T cells.  Although NKG2D plays an important role in mediating immune responses in autoimmune and infectious diseases, cancer, and transplantation, and is an attractive target for therapeutic intervention, monoclonal antibodies to NKG2D that are suitable for clinical investigations have not been available.

This invention describes a fully human monoclonal antibody (KYK-2.0 IgG1) with high specificity and affinity to human NKG2D.  In solution, KYK-2.0 IgG1 interferes with the cytolytic activity of human NK cells.  When immobilized, KYK-2.0 IgG1 induces human NK cell activation.  The dual antagonistic and agonistic activity promises a broad range of therapeutic applications including, autoimmune and infectious diseases, cancer, and transplantation.
 
Further R&D Needed:

• Conduct additional preclinical analysis to further characterize the antibody in terms of activating, neutralizing, or depleting activity toward NKG2D-expressing cells

• Develop in vitro and in vivo models of autoimmune and infectious diseases, cancer, and transplantation for preclinical evaluation

• Establish a mammalian cell line for stable expression of KYK-2.0 IgG1

• Generate bispecific antibodies that employ the monoclonal antibody as NK and CD8+ T cell recruiting moiety

• Investigate these bispecific antibodies in in vitro and in vivo models of cancer

• Fully human monoclonal antibody for a variety of indications including autoimmune and infectious disease, cancer, and transplantation

• Ability to develop broad and potent therapeutic utility due to dual antagonistic and agonistic activity and low immunogenicity